The Penn Diabetes and Endocrinology Research Center (DERC) participates in the nationwide inter-disciplinary program established over two decades ago by the NIDDK to foster research and training in the areas of diabetes and related endocrine and metabolic disorders. The Penn DERC is located at and administered by the University of Pennsylvania. It serves 65 diabetes-oriented investigators primarily from the University of Pennsylvania School of Medicine, but also from other Schools within the University of Pennsylvania as well as additional Philadelphia institutions including Jefferson and Temple. The Penn DERC is highly interactive and interdisciplinary, representing many basic science and clinical departments at Penn and the other institutions. The Research Base of the Penn DERC includes investigators organized in the following 4 focus groups: Beta-cell Physiology and Pathology; Signaling by Insulin and Other Hormones; Genetics and Complications of Diabetes; and Obesity, Metabolism, and Nutrition. The Penn DERC facilitates and supports research in diabetes and endocrinology in a variety of ways. Seven Biomedical Research Core facilities are designed to facilitate the inter-disciplinary investigations of Penn DERC scientists: Biomedical Imaging Core; Functional Genomics Core; Islet Cell Biology Core, Mouse Phenotyping, Metabolism, and Physiology Core; Radioimmunoassay Core; Transgenic and Chimeric Animal Core, and Viral Vector Core. A Pilot and Feasibility Grant Program that has been extremely successful for over two decades serves to nurture new investigators in diabetes and to foster new initiatives in diabetes. An intensive Academic Enrichment Program organizes Diabetes and Endocrinology Research seminars and an annual Diabetes Day symposium as well as other activities that facilitate communication and collaboration of Penn DERC investigators while keeping them abreast of the latest discoveries in diabetes and endocrinology. Penn DERC investigators mentor trainees at every level (undergraduate, predoctoral, and post-doctoral Ph.D., M.D., and combined M.D./Ph.D.), and the DERC academic activities provide a superb environment for training in diabetes research. An Administrative Component coordinates and publicizes the Biomedical Cores, Pilot and Feasibility Grant Program, and Academic Enrichment Program. These functions of the Penn DERC maintain the diabetes-related research program at this Center at the forefront of biomedical science. Moreover, the present Center grant (NIDDK19525) remains the foundation of inter-disciplinary diabetes research in Philadelphia.